Regulated spindle orientation buffers tissue growth in the epidermis.

dc.contributor.author

Morrow, Angel

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Underwood, Julie

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Seldin, Lindsey

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Hinnant, Taylor

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Lechler, Terry

dc.date.accessioned

2022-09-28T21:25:53Z

dc.date.available

2022-09-28T21:25:53Z

dc.date.issued

2019-10

dc.date.updated

2022-09-28T21:25:43Z

dc.description.abstract

Tissue homeostasis requires a balance between progenitor cell proliferation and loss. Mechanisms that maintain this robust balance are needed to avoid tissue loss or overgrowth. Here we demonstrate that regulation of spindle orientation/asymmetric cell divisions is one mechanism that is used to buffer changes in proliferation and tissue turnover in mammalian skin. Genetic and pharmacologic experiments demonstrate that asymmetric cell divisions were increased in hyperproliferative conditions and decreased under hypoproliferative conditions. Further, active K-Ras also increased the frequency of asymmetric cell divisions. Disruption of spindle orientation in combination with constitutively active K-Ras resulted in massive tissue overgrowth. Together, these data highlight the essential roles of spindle orientation in buffering tissue homeostasis in response to perturbations.

dc.identifier

48482

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2050-084X

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2050-084X

dc.identifier.uri

https://hdl.handle.net/10161/25870

dc.language

eng

dc.publisher

eLife Sciences Publications, Ltd

dc.relation.ispartof

eLife

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10.7554/elife.48482

dc.subject

Epidermis

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Stem Cells

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Skin

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Animals

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Mice

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Cell Division

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Cell Proliferation

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Cell Polarity

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Homeostasis

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Proto-Oncogene Proteins p21(ras)

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Asymmetric Cell Division

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Spindle Apparatus

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Epidermal Cells

dc.title

Regulated spindle orientation buffers tissue growth in the epidermis.

dc.type

Journal article

duke.contributor.orcid

Hinnant, Taylor|0000-0002-8912-6851

pubs.begin-page

e48482

pubs.organisational-group

Duke

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School of Medicine

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Student

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Basic Science Departments

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Clinical Science Departments

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Institutes and Centers

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Cell Biology

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Dermatology

pubs.organisational-group

Duke Cancer Institute

pubs.organisational-group

Regeneration Next Initiative

pubs.publication-status

Published

pubs.volume

8

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